Autism spectrum disorder (ASD) is a complex, multifactorial disorder, the prevalence of which is rising. Specific biomarkers are yet to be identified for the classic ASD phenotypes, so despite treatment advances, most interventions focus on the comorbid disorders of ASD and have little impact on the underlying pathogenesis of the disorder. This article describes drug treatments that target the core symptoms of ASD and its comorbid conditions in children and adolescents. Difficulties and challenges encountered when treating the most frequent comorbidities are discussed, with emphasis on the safety, tolerability and efficacy of medications. In view of its widespread use, complementary and alternative medicine is also described.